AM Resistance

1. Target not present- Mycoplasma sp has no cell wall. Lactobacillus sp. side chain in cell wall and glycopeptides cannot bind.
2. Target not accessible- Vancomycin unable to penetrate Gram negative bacteria's outer membrane.
3. Developmental structure/ state- C. difficile spore- persister cells and biofilms more resistant
4. Metabolism- metronidazole uptake and action require anaerobic conditions.

Exposure to antibiotics in the environment encourages resistance as small numbers of ‘resistant mutants’ will survive whilst susceptible organisms die off

• Particularly likely to happen in the gut of someone taking antibiotics or in bacteria in a hospital environment

Change in bacterial DNA gives it the ability to become resistant to the antibiotic.

1. Genetic mutation- misreading of DNA, bacteria reproducing rapidly has a scope of error in reading.
2. Transfer of bacterial DNA

1. Bacterial transformation- - when bacteria die and the cells break apart, ‘free-floating’ DNA released into surrounding environment may be ‘scavenged’ by other bacteria and incorporated into DNA - the DNA may contain genes for antibiotic resistance
2. Conjugation: replication and transfer of plasmid DNA - plasmid DNA may contain genes for resistance
3. Transduction: bacterial DNA transferred from one bacterium to the other inside a virus that infects bacteria (bacteriophages)

1. Altered permeability
2. Drug inactivating enzymes
3. Drug target modification
4. Target replication

It can be categorised into altered influx due to changes in the outer membrane or active efflux where the energy dependant pump helps the bacteria push the antibiotic out of the cell.

• Bacteria may possess genes which code for enzymes that chemically degrade or inactivate the antibiotic
• β -lactamases and cephalosporinases target and disrupt the β-lactam ring of the antibiotics.
• ESBLs: Extended Spectrum Beta Lactamase enzymes that inactive almost all penicillins and cephalosporins
  • Produced by some Gram-negative bacteria

Beta lactamases are a large family of enzymes that degrade beta lactate antibiotics. Clavulanic acid and Tazobactam are some examples of inhibitors.

1. Penicillinase (resistance to early penicillins like amoxycillin)
2. Cephalosporinase
3. Extended spectrum beta Lactamase- resistance to all penicillins and unto 3rd gen cephalosporins and monobactams.
4. Carbapenemase (resistance to all penicillins, cephalosporins and carbapenems)

The altered target site like modifications in subunits of 30S and 50S ribosome causes the target where antibiotic works to be changed, which thus renders the antibiotic ineffective.